Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers

doi:10.1093/jmcb/mjw016

	Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers
	Sa, Rina 1,2; Zhang, Wanwei 2,3; Ge, Jing 2,3; Wei, Xinben 1,2; Zhou, Yunhua 1; Landzberg, David R.4; Wang, Zhenzhen 1; Han, Xianlin 5; Chen, Luonan2,3,6 ; Yin, Huiyong1,2,6,7
	2016-06
发表期刊	JOURNAL OF MOLECULAR CELL BIOLOGY (IF:5.3[JCR-2023],6.1[5-Year])
ISSN	1674-2788
卷号	8 期号:3 页码:195-206
发表状态	已发表
DOI	10.1093/jmcb/mjw016
摘要	Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for type 2 diabetes and metabolic syndrome. However, accurately differentiating nonalcoholic steatohepatitis (NASH) from hepatosteatosis remains a clinical challenge. We identified a critical transition stage (termed pre-NASH) during the progression from hepatosteatosis to NASH in a mouse model of high fat-induced NAFLD, using lipidomics and a mathematical model termed dynamic network biomarkers (DNB). Different from the conventional biomarker approach based on the abundance of molecular expressions, the DNB model exploits collective fluctuations and correlations of different metabolites at a network level. We found that the correlations between the blood and liver lipid species drastically decreased after the transition from steatosis to NASH, which may account for the current difficulty in differentiating NASH from steatosis based on blood lipids. Furthermore, most DNB members in the blood circulation, especially for triacylglycerol (TAG), are also identified in the liver during the disease progression, suggesting a potential clinical application of DNB to diagnose NASH based on blood lipids. We further identified metabolic pathways responsible for this transition. Our study suggests that the transition from steatosis to NASH is not smooth and the existence of pre-NASH may be partially responsible for the current clinical limitations to diagnose NASH. If validated in humans, our study will open a new avenue to reliably diagnose pre-NASH and achieve early intervention of NAFLD.
关键词	nonalcoholic fatty liver disease (NAFLD) mass spectrometry lipidomics systems biology pre-NASH dynamical network biomarkers
收录类别	SCI
语种	英语
资助项目	Hundred Talents Program from CAS[2012OHTP07]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000380253100003
出版者	OXFORD UNIV PRESS
WOS关键词	FATTY LIVER-DISEASE ; IDENTIFYING CRITICAL TRANSITIONS ; EARLY-WARNING SIGNALS ; COMPLEX DISEASES ; SHOTGUN LIPIDOMICS ; HEPATIC STEATOSIS ; MASS-SPECTROMETRY ; BIOLOGICAL SAMPLES ; EDGE BIOMARKERS ; SINGLE-SAMPLE
原始文献类型	Article
引用统计	被引频次：28[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1812
专题	生命科学与技术学院_特聘教授组_陈洛南组生命科学与技术学院_特聘教授组_尹慧勇组
通讯作者	Chen, Luonan; Yin, Huiyong
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Food Safety Res, Shanghai 200031, Peoples R China 2.Univ Chinese Acad Sci, CAS, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Key Lab Syst Biol, Innovat Ctr Cell Signaling Network, Inst Biochem & Cell Biol,SIBS, Shanghai 200031, Peoples R China 4.Vanderbilt Univ Sch Med, Nashville, TN 37235 USA 5.Sanford Burnham Med Res Inst, Diabet & Obes Res Ctr, Orlando, FL 32827 USA 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 7.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing 100021, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Sa, Rina,Zhang, Wanwei,Ge, Jing,et al. Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2016,8(3):195-206.
APA	Sa, Rina.,Zhang, Wanwei.,Ge, Jing.,Wei, Xinben.,Zhou, Yunhua.,...&Yin, Huiyong.(2016).Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers.JOURNAL OF MOLECULAR CELL BIOLOGY,8(3),195-206.
MLA	Sa, Rina,et al."Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers".JOURNAL OF MOLECULAR CELL BIOLOGY 8.3(2016):195-206.